PTSD and the Default Network: Developing Imaging Phenotypes

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DESCRIPTION (provided by applicant): The aim of this career development proposal is to explore neuroimaging correlates of Post-Traumatic Stress Disorder (PTSD) on the Default Network (DN), as a vehicle to train the candidate for a career in PTSD neuroimaging research. The candidate will use three separate and complementary means to examine the effects of PTSD on the DN, by evaluating changes in resting state functional connectivity, task-induced deactivations, and white matter integrity utilizing diffusion tensor imaging (DTI) in a group of subjects with the disorder for comparison with an appropriate control group. The candidate is guided by previous research in these areas in civilian PTSD; given the potential of this research it is critical to investigate these findingsin Veteran populations. The candidate's long-term career goal is to investigate the DN as a potential prognostic tool for PTSD: to predict those at risk for developing PTSD after trauma exposure and develop metrics to measure, or predict, treatment response. The candidate's immediate career goals are to use this proposal to learn the research skills needed to pursue an independent career in clinically informed neuroimaging in Veterans. The central hypothesis of this career award is that PTSD adversely affects the medial prefrontal cortex (MPFC), a node of the DN, which in turn leads to network-level effects that contribute to the clinical symptoms of PTSD. The candidate will evaluate this hypothesis using three Specific Aims; that Veterans with combat associated PTSD have 1) decreased resting state functional DN connectivity, 2) increased magnitude of task-associated DN deactivations, and 3) decreased integrity of white matter tracts connecting DN regions, compared to Veterans without PTSD. To accomplish these aims, the candidate will pursue a careful training plan under the expert tutelage of a transdisciplinary mentoring team. This approach is innovative, as it explores different yet complementary means to evaluate the DN, and is significant because it may lead to identification of possible biomarkers of PTSD with many potential applications to improve our Veterans' health. The focused impact of this proposal is that it pursues research in the service of the candidate's training, to bring a young investigator to the VA for a career in independently funded PTSD neuroimaging research.